JP2016193932A - Cd3特異的結合ドメインによって引き起こされる有害作用の予防 - Google Patents
Cd3特異的結合ドメインによって引き起こされる有害作用の予防 Download PDFInfo
- Publication number
- JP2016193932A JP2016193932A JP2016133918A JP2016133918A JP2016193932A JP 2016193932 A JP2016193932 A JP 2016193932A JP 2016133918 A JP2016133918 A JP 2016133918A JP 2016133918 A JP2016133918 A JP 2016133918A JP 2016193932 A JP2016193932 A JP 2016193932A
- Authority
- JP
- Japan
- Prior art keywords
- binding domain
- dose
- day
- use according
- administration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000002411 adverse Effects 0.000 title claims abstract description 59
- 230000002265 prevention Effects 0.000 title claims abstract description 9
- 230000000694 effects Effects 0.000 title description 49
- 230000009870 specific binding Effects 0.000 title description 3
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims abstract description 130
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims abstract description 130
- 230000027455 binding Effects 0.000 claims abstract description 91
- 239000003862 glucocorticoid Substances 0.000 claims abstract description 69
- 230000000926 neurological effect Effects 0.000 claims abstract description 59
- 238000011282 treatment Methods 0.000 claims abstract description 56
- 229960003957 dexamethasone Drugs 0.000 claims description 53
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 53
- 229960003008 blinatumomab Drugs 0.000 claims description 29
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 12
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 10
- 206010044565 Tremor Diseases 0.000 claims description 7
- 206010003591 Ataxia Diseases 0.000 claims description 5
- 206010019233 Headaches Diseases 0.000 claims description 5
- 231100000869 headache Toxicity 0.000 claims description 5
- 206010048962 Brain oedema Diseases 0.000 claims description 4
- 208000006752 brain edema Diseases 0.000 claims description 4
- 208000004209 confusion Diseases 0.000 claims description 4
- 206010013395 disorientation Diseases 0.000 claims description 4
- 206010010904 Convulsion Diseases 0.000 claims description 3
- 230000036461 convulsion Effects 0.000 claims description 3
- 208000014644 Brain disease Diseases 0.000 claims description 2
- 208000004547 Hallucinations Diseases 0.000 claims description 2
- 206010033799 Paralysis Diseases 0.000 claims description 2
- 208000020764 Sensation disease Diseases 0.000 claims description 2
- 208000027765 speech disease Diseases 0.000 claims description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 51
- 238000000034 method Methods 0.000 description 36
- 230000004044 response Effects 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 17
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 16
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 16
- 125000003275 alpha amino acid group Chemical group 0.000 description 14
- 108090000623 proteins and genes Proteins 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 210000003169 central nervous system Anatomy 0.000 description 11
- 238000001802 infusion Methods 0.000 description 11
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 9
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 9
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 150000007523 nucleic acids Chemical group 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- 206010025323 Lymphomas Diseases 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 6
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 6
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 6
- -1 clopredonol Chemical compound 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229960004544 cortisone Drugs 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 230000003211 malignant effect Effects 0.000 description 6
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 229960005205 prednisolone Drugs 0.000 description 5
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 5
- 230000000069 prophylactic effect Effects 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 201000003444 follicular lymphoma Diseases 0.000 description 4
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 3
- 206010003062 Apraxia Diseases 0.000 description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 3
- 108091008874 T cell receptors Proteins 0.000 description 3
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 3
- 238000009175 antibody therapy Methods 0.000 description 3
- 210000001185 bone marrow Anatomy 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 206010052015 cytokine release syndrome Diseases 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229960000289 fluticasone propionate Drugs 0.000 description 3
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101100383038 Homo sapiens CD19 gene Proteins 0.000 description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- 206010060860 Neurological symptom Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229960002537 betamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 210000001165 lymph node Anatomy 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960002117 triamcinolone acetonide Drugs 0.000 description 2
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- HKZAAJSTFUZYTO-LURJTMIESA-N (2s)-2-[[2-[[2-[[2-[(2-aminoacetyl)amino]acetyl]amino]acetyl]amino]acetyl]amino]-3-hydroxypropanoic acid Chemical compound NCC(=O)NCC(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O HKZAAJSTFUZYTO-LURJTMIESA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 102100036775 Afadin Human genes 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 102000008102 Ankyrins Human genes 0.000 description 1
- 108010049777 Ankyrins Proteins 0.000 description 1
- 108020005098 Anticodon Proteins 0.000 description 1
- 208000006740 Aseptic Meningitis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000028564 B-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 101000984722 Bos taurus Pancreatic trypsin inhibitor Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 1
- 101100454808 Caenorhabditis elegans lgg-2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 206010010301 Confusion and disorientation Diseases 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- 101100016370 Danio rerio hsp90a.1 gene Proteins 0.000 description 1
- 101100285708 Dictyostelium discoideum hspD gene Proteins 0.000 description 1
- 101100125027 Dictyostelium discoideum mhsp70 gene Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102100033417 Glucocorticoid receptor Human genes 0.000 description 1
- 102000018932 HSP70 Heat-Shock Proteins Human genes 0.000 description 1
- 108010027992 HSP70 Heat-Shock Proteins Proteins 0.000 description 1
- 101150031823 HSP70 gene Proteins 0.000 description 1
- 101710113864 Heat shock protein 90 Proteins 0.000 description 1
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 1
- 101000926939 Homo sapiens Glucocorticoid receptor Proteins 0.000 description 1
- 101000582320 Homo sapiens Neurogenic differentiation factor 6 Proteins 0.000 description 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010036650 Immunoproteins Proteins 0.000 description 1
- 102000012214 Immunoproteins Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 102000019298 Lipocalin Human genes 0.000 description 1
- 108050006654 Lipocalin Proteins 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 206010027201 Meningitis aseptic Diseases 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 102100030589 Neurogenic differentiation factor 6 Human genes 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 101710160107 Outer membrane protein A Proteins 0.000 description 1
- 102000000470 PDZ domains Human genes 0.000 description 1
- 108050008994 PDZ domains Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000007542 Paresis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010037180 Psychiatric symptoms Diseases 0.000 description 1
- 101100071627 Schizosaccharomyces pombe (strain 972 / ATCC 24843) swo1 gene Proteins 0.000 description 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 102000002933 Thioredoxin Human genes 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000009831 antigen interaction Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000003913 calcium metabolism Effects 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 150000001887 cortisones Chemical class 0.000 description 1
- 231100000409 cytocidal Toxicity 0.000 description 1
- 230000000445 cytocidal effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 101150052825 dnaK gene Proteins 0.000 description 1
- 150000002084 enol ethers Chemical class 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002373 hemiacetals Chemical class 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000016290 incoordination Diseases 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 231100000897 loss of orientation Toxicity 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 239000002395 mineralocorticoid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 229940037129 plain mineralocorticoids for systemic use Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 239000002795 scorpion venom Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Developing Agents For Electrophotography (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Materials For Medical Uses (AREA)
- Steroid Compounds (AREA)
Abstract
Description
本発明は、この要求に取り組むものであり、そしてCD19×CD3二重特異性抗体のようなCD3結合ドメインによって引き起こされる神経学的有害作用の改善、治療、又は予防における使用のための手段及び方法に関して実施例を提供するものである。
これらの実施例は、本明細書において特徴付けられ及び記載されて、特許請求の範囲に反映される。
別段の指示がない限り、一連の要素に先行する「少なくとも」という用語は、その一連のすべての要素を指すと理解されるべきである。当業者であれば、本明細書に記載されている発明の具体的な態様の均等物を多数理解できる又はありふれた実験手段だけ用いればそれらを確認することができるだろう。そのような均等物は、本発明に包含されることが意図されている。
本明細書の各場合において、「含んでいる(comprising)」、「から本質的に成っている(consisting essentially of)」及び「から成っている(consisting of)」のどの用語も、他の2つの用語のうちどちらかと置き換えられてよい。
そして、本発明は、CD3結合ドメインによって引き起こされる神経学的有害作用の改善、治療、又は予防の方法にも関連しており、該方法は、グルココルチコイド(GC)を必要とする患者にそれを投与することを含む。該GCは、好ましくは、該CD3結合ドメインによって引き起こされる神経学的有害作用を改善、治療、又は予防するのに十分な量で投与される。
さらに好ましい態様では、前記GCは、デキサメタゾンである。
しかし、本発明者らはまた、後で高用量まで上昇させない均一の用量による継続的投与を採用できるように、DLBCLによって引き起こされるリンパ節組織の腫瘍塊及び/又は節外性リンパ腫の治療を検討した。例えば、本治療計画は、耐容性が良好で有害作用がないときは8週(56日)までの治療過程の終了まで、そして安全かつ有効であると確定された場合にはさらに長期に、5μg/m2/24時、15μg/m2/24時、又は60μg/m2/24時でCD19×CD3二重特異性単鎖抗体を投与することを含む。
該患者は、1:5未満のB/T細胞比で特徴付けられる(PCT/EP2010/066207号を参照)ことも想定されている。
ヒトCD3イプシロンに結合するCD3結合分子が好ましい。国際公開第2008/119567号又は国際公開第2008/119566号に極めて詳細に開示されているCD3イプシロンエピトープがより好ましい。
さらに好ましい態様では、本発明は、ヒトCD3イプシロン鎖のエピトープに結合できる第1の結合ドメイン及びヒトCD19に結合できる第2の結合ドメインを含むCD19×CD3二重特異性抗体を用いた治療/投与計画の方法に関連する。本発明の方法に従った二重特異性分子の例は、国際公開第99/54440号、国際公開第2004/106381号、及び国際公開第2008/119565号に極めて詳細に記載されている。変異体、断片、均等物などを含む、これらに開示されているすべての特定のCD19×CD3二重特異性抗体は、特に好ましい本発明のCD19×CD3二重特異性抗体である。
ヒトCD19タンパク質は、GenBankアクセッション番号AAA69966に示されている。
しかしながら、本発明の方法は、
VH(CD19)−VL(CD19)−VH(CD3)−VL(CD3)、
VL(CD19)−VH(CD19)−VL(CD3)−VH(CD3)、
VH(CD19)−VL(CD19)−VL(CD3)−VH(CD3)、
VL(CD3)−VH(CD3)−VH(CD19)−VL(CD19)、
VH(CD3)−VL(CD3)−VH(CD19)−VL(CD19)、
VL(CD3)−VH(CD3)−VL(CD19)−VH(CD19)、又は、
VH(CD3)−VL(CD3)−VL(CD19)−VH(CD19)
のような他のドメイン配置のCD19×CD3二重特異性単鎖抗体でも実施できることが想定されている。
(a)配列番号11(RYTMH)のCD3 CDR−H1、より好ましくは配列番号11(GYTFTRYTMH)、配列番号12(YINPSRGYTNYNQKFKD)のCD3 CDR−H2、及び、配列番号13(YYDDHYCLDY)のCD3 CDR−H3として示されている重鎖の抗CD3 CDR、並びに/又は、
(b)配列番号14(RASSSVSYMN)のCD3 CDR−L1、配列番号15(DTSKVAS)のCD3 CDR−L2、及び、配列番号16(QQWSSNPLT)のCD3 CDR−L3として示されている軽鎖の抗CD3 CDR、並びに/又は、
(c)配列番号17(SYWMN)のCD19 CDR−H1、より好ましくは配列番号17(GYAFSSYWMN)、配列番号18(QIWPGDGDTNYNGKFKG)のCD19 CDR−H2、及び、配列番号19(RETTTVGRYYYAMDY)のCD19 CDR−H3として示されるような重鎖の抗CD19 CDR、並びに/又は、
(d)配列番号20(KASQSVDYDGDSYLN)のCD19 CDR−L1、配列番号21(DASNLVS)のCD19 CDR−L2、及び、配列番号22(QQSTEDPWT)のCD19 CDR−L3として示されるような軽鎖の抗CD19 CDRを含む。
本明細書でいうCDRは、Kabat番号方式に従う。Kabat番号付けスキームは、抗体中の残基を一貫した方法で番号付けするために広く採用されている基準である(Kabatら、Sequences of Proteins of Immunological Interest、1991)。
(a)配列番号3(配列番号4で示される核酸配列)で示されるCD19可変重鎖、及び/又は、
(b)配列番号5(配列番号6で示される核酸配列)で示されるCD19可変軽鎖、及び/又は、
(c)配列番号7(配列番号8で示される核酸配列)で示されるCD3可変重鎖、及び/又は、
(d)配列番号9(配列番号10で示される核酸配列)で示されるCD3可変軽鎖
を含むことが好ましい。
より好ましくは、本発明の方法に適用されるCD19×CD3二重特異性抗体は、CD19可変重鎖及び軽鎖並びに/又はCD3可変重鎖及び軽鎖を含む。さらに好ましくは、本発明の方法に適用されるCD19×CD3二重特異性抗体は、CD19可変重鎖及び軽鎖もCD3可変重鎖及び軽鎖も含む。
(a)配列番号1で表現されるようなアミノ酸配列、
(b)配列番号2で示される核酸配列によってコードされたアミノ酸配列、
(c)(b)の核酸配列に少なくとも70%、80%、90%、95%、又は99%相同な核酸配列によってコードされたアミノ酸配列であって、特異的にCD3及びCD19に結合することができる該アミノ酸配列、並びに、
(d)遺伝子コードの結果として(b)のヌクレオチド配列と縮重した核酸配列によってコードされたアミノ酸配列であって、特異的にCD3及びCD19に結合することができる該アミノ酸配列
から成る群から選択されるアミノ酸配列を含むことも好ましい。
国際公開第99/54440号に記載されているCD19×CD3二重特異性抗体であるMT103も、国際公開第2004/106381号及び国際公開第2008/119565号に記載されているCD19×CD3二重特異性抗体も、特に好ましい。
本発明はさらに、
(i)CD19×CD3二重特異性抗体のようなCD3結合ドメインをヒト患者に投与するための、又は、
(ii)CD3結合ドメインを投与することで、ヒト患者の悪性CD19陽性リンパ球を治療するための
方法に関連しているおり、該抗体は、GCの前に、これに続いて、及び/又は、これと同時に投与されるべきである。
「上回る」という用語は、第2の期間が第1の期間よりも少なくとも1日長いことを意味する。
好ましくは、ALLの完全寛解は、骨髄中5%以下の芽球数及び骨髄機能の回復と定義されている。NHL患者における詳しい寛解及び奏効の定義は、Chesonら、1999、J Clin Oncol.4月、17(4):1244に従って用いられる。
治療のためのデキサメタゾンの投与は、ブリナツモマブによる治療を中断せずに神経学的及び/又は精神医学的症状が消失するという点で有益だった。
神経学的有害事象を和らげるためのデキサメタゾンの治療的使用に加えて、デキサメタゾンはまた、神経学的有害事象を予防するための予防方法としても使用される。
患者108−007は、神経学的/精神医学的有害事象によって中断する必要はなかった。この患者は、リンパ腫の完全寛解を達成した。
患者108−008は、神経学的/精神医学的有害事象によって中断する必要はなかった。
患者108−009は、神経学的/精神医学的有害事象によって中断する必要はなかった。この患者は、リンパ腫の客観的奏効を達成した。
患者108−010は、注入開始の1時間前に、追加で100mgのプレドニゾロンを受けた。該患者は、神経学的/精神医学的有害事象によって中断する必要はなかった。
それぞれ6人のDLBCL患者からなる2群が登録された。該2群は、有害事象の緩和のために抗体注入の開始時に投与されたグルココルチコイド療法の用量及びスケジュールという点でだけ異なっていた。
12人の患者のうち、5人が男性で7人が女性だった。年齢の中央値は57歳(24〜78歳の範囲)だった。患者は、中央値4(2〜6の範囲)の先の投薬計画を受けた。すべての患者はリツキシマブにさらされた。12人中8人の患者はASCTを経験した。スクリーニング時の国際予後指標(IPI)は、中央値2で1〜3の範囲に及んでいた。第1群においては、開始1時間前に100mgのプレドニゾロンが投与され、第2群においては、患者は第1、2、及び3日にデキサメタゾン(3×8mg)を受けた。第2群の治療開始前には、CD19×CD3二重特異性抗体構築物の投与より12時間前及び1時間前に、20mgのデキサメタゾンが投与された。
また、「早期デキサメタゾン」の患者においては、客観的奏効が観察された。
Claims (14)
- CD3結合ドメイン(の投与)によって引き起こされる神経学的有害事象の改善、治療、又は予防における使用のためのグルココルチコイド(GC)。
- 前記GCが、デキサメタゾンである、請求項1に記載の使用。
- 前記GCが、CD結合ドメインの前に、これに続いて、又は、これと組み合わせて投与される、請求項1又は2に記載の使用。
- 第1の用量のCD結合ドメインが第1の期間に投与され、これに引き続いて第2の用量のCD結合ドメインが第2の期間に投与され、該第2の用量が第1の用量を上回る、請求項1〜3のいずれか1項に記載の使用。
- 第1及び第2の期間における第1及び第2の用量のCD結合ドメインの投与後に、第3の用量のCD結合ドメインを投与し、該第3の用量が第1及び第2の用量を上回る、請求項4に記載の使用。
- 前記GCが、第1の用量のCD結合ドメインの投与の前、並びに、第2及び/又は第3のCD結合ドメインの投与の前に投与される、請求項4又は5に記載の使用。
- 前記神経学的有害事象が、感覚障害、けいれん、脳障害、脳浮腫、錯乱、運動失調、失行症、発話障害、幻覚、不全麻痺、振戦、頭痛又は見当識障害の1種又はそれ以上である、請求項1〜6のいずれか1項に記載の使用。
- 前記GCが、神経学的有害事象の発現に続いて投与される、請求項1〜7のいずれか1項に記載の使用。
- 前記CD3結合ドメインが、二重特異性単鎖抗体である、請求項1〜8のいずれか1項に記載の使用。
- 前記二重特異性単鎖抗体が、CD19×CD3二重特異性単鎖抗体である、請求項9に記載の使用。
- 前記CD19×CD3二重特異性単鎖抗体が、MT103である、請求項10に記載の使用。
- 患者がヒトである、請求項1〜11のいずれか1項に記載の使用。
- 患者が1:5未満のB/T細胞比で特徴付けられる、請求項1〜12のいずれか1項に記載の使用。
- GC及びCD3結合ドメイン、並びに、該GCが該CD3結合ドメインによって引き起こされる神経学的有害事象の治療、改善、及び/又は予防のために用いられるべきことを示す使用説明書及び/又は印を含む、キット。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US41222910P | 2010-11-10 | 2010-11-10 | |
US61/412,229 | 2010-11-10 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013538125A Division JP6023717B2 (ja) | 2010-11-10 | 2011-10-27 | Cd3特異的結合ドメインによって引き起こされる有害作用の予防 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2016193932A true JP2016193932A (ja) | 2016-11-17 |
JP2016193932A5 JP2016193932A5 (ja) | 2017-06-08 |
JP6189491B2 JP6189491B2 (ja) | 2017-08-30 |
Family
ID=45044532
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013538125A Active JP6023717B2 (ja) | 2010-11-10 | 2011-10-27 | Cd3特異的結合ドメインによって引き起こされる有害作用の予防 |
JP2016133918A Active JP6189491B2 (ja) | 2010-11-10 | 2016-07-06 | Cd3特異的結合ドメインによって引き起こされる有害作用の予防 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013538125A Active JP6023717B2 (ja) | 2010-11-10 | 2011-10-27 | Cd3特異的結合ドメインによって引き起こされる有害作用の予防 |
Country Status (30)
Country | Link |
---|---|
US (2) | US10130638B2 (ja) |
EP (3) | EP3831386A1 (ja) |
JP (2) | JP6023717B2 (ja) |
KR (1) | KR101891845B1 (ja) |
CN (2) | CN103533943B (ja) |
AU (3) | AU2011328393B2 (ja) |
CA (1) | CA2816668C (ja) |
CL (1) | CL2013001287A1 (ja) |
CR (1) | CR20130278A (ja) |
CY (1) | CY1118894T1 (ja) |
DK (1) | DK2637670T4 (ja) |
EA (1) | EA026075B1 (ja) |
ES (2) | ES2842937T3 (ja) |
FI (1) | FI2637670T4 (ja) |
HR (1) | HRP20170814T4 (ja) |
HU (1) | HUE032782T2 (ja) |
IL (2) | IL226268B (ja) |
LT (1) | LT2637670T (ja) |
MA (1) | MA34726B1 (ja) |
ME (1) | ME02722B (ja) |
MY (1) | MY173177A (ja) |
NZ (1) | NZ610034A (ja) |
PL (1) | PL2637670T5 (ja) |
PT (1) | PT2637670T (ja) |
RS (1) | RS55995B2 (ja) |
SG (2) | SG190174A1 (ja) |
SI (1) | SI2637670T2 (ja) |
TN (1) | TN2013000250A1 (ja) |
UA (1) | UA113397C2 (ja) |
WO (1) | WO2012062596A1 (ja) |
Families Citing this family (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2417065T3 (es) | 2005-04-26 | 2013-08-05 | Trion Pharma Gmbh | Combinación de anticuerpos con glucocorticoides para el tratamiento del cáncer |
FI2637670T4 (fi) | 2010-11-10 | 2024-03-19 | Amgen Research Munich Gmbh | Cd3-spesifisten sitoutumisdomeenien aiheuttamien haittavaikutusten estäminen |
EP2701741B1 (en) * | 2011-04-28 | 2020-06-10 | Amgen Research (Munich) GmbH | Dosage regimen for administering a cd19xcd3 bispecific antibody to patients at risk for potential adverse effects |
US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
CN105051069B (zh) | 2013-01-14 | 2019-12-10 | Xencor股份有限公司 | 新型异二聚体蛋白 |
US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
JO3529B1 (ar) * | 2013-02-08 | 2020-07-05 | Amgen Res Munich Gmbh | مضاد التصاق خلايا الدم البيض من أجل التخفيف من الاثار السلبية الممكنة الناتجة عن مجالات ارتباط cd3- المحدد |
LT2951203T (lt) * | 2013-03-15 | 2019-09-10 | Xencor, Inc. | Heterodimeriniai baltymai |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
US10544187B2 (en) | 2013-03-15 | 2020-01-28 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
LT3083689T (lt) | 2013-12-17 | 2020-08-10 | Genentech, Inc. | Anti-cd3 antikūnai ir jų panaudojimo būdai |
EA201691925A1 (ru) | 2014-03-28 | 2017-06-30 | Ксенкор, Инк. | Биспецифические антитела, которые связываются с cd38 и cd3 |
SG10201804931QA (en) | 2014-09-12 | 2018-07-30 | Genentech Inc | Anti-cll-1 antibodies and immunoconjugates |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
DK3223845T3 (da) | 2014-11-26 | 2021-08-16 | Xencor Inc | Heterodimere antistoffer, der binder cd3 og cd20 |
KR20170086549A (ko) | 2014-12-05 | 2017-07-26 | 제넨테크, 인크. | 항-CD79b 항체 및 이용 방법 |
WO2016105450A2 (en) | 2014-12-22 | 2016-06-30 | Xencor, Inc. | Trispecific antibodies |
WO2016141387A1 (en) | 2015-03-05 | 2016-09-09 | Xencor, Inc. | Modulation of t cells with bispecific antibodies and fc fusions |
US10501545B2 (en) | 2015-06-16 | 2019-12-10 | Genentech, Inc. | Anti-CLL-1 antibodies and methods of use |
KR20180023952A (ko) | 2015-06-16 | 2018-03-07 | 제넨테크, 인크. | FcRH5에 대한 인간화 및 친화도 성숙 항체 및 사용방법 |
CA2991799A1 (en) | 2015-07-15 | 2017-01-19 | Zymeworks Inc. | Drug-conjugated bi-specific antigen-binding constructs |
TWI796283B (zh) | 2015-07-31 | 2023-03-21 | 德商安美基研究(慕尼黑)公司 | Msln及cd3抗體構築體 |
TWI829617B (zh) | 2015-07-31 | 2024-01-21 | 德商安美基研究(慕尼黑)公司 | Flt3及cd3抗體構築體 |
TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究(慕尼黑)公司 | Egfrviii及cd3抗體構築體 |
CN106810611A (zh) * | 2015-11-30 | 2017-06-09 | 中国科学院深圳先进技术研究院 | 抗cMet和CD3特异性双靶向抗体及其制备方法和应用、含该双靶向抗体表达盒的微环DNA及应用 |
CN106810610A (zh) * | 2015-11-30 | 2017-06-09 | 中国科学院深圳先进技术研究院 | 抗EpCAM和CD3特异性双靶向抗体及其制备方法和应用、含该双靶向抗体表达盒的微环DNA及应用 |
EP3387013B1 (en) | 2015-12-07 | 2022-06-08 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and psma |
EA039859B1 (ru) * | 2016-02-03 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
SG11201806150RA (en) | 2016-02-03 | 2018-08-30 | Amgen Res Munich Gmbh | Psma and cd3 bispecific t cell engaging antibody constructs |
CN110352070B (zh) | 2016-06-14 | 2024-09-17 | Xencor股份有限公司 | 双特异性检查点抑制剂抗体 |
CN109715663B (zh) | 2016-06-28 | 2022-11-25 | Xencor股份有限公司 | 结合生长抑素受体2的异源二聚抗体 |
US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
BR112019007288A2 (pt) | 2016-10-14 | 2019-07-09 | Xencor Inc | proteína heterodimérica biespecífica, composições de ácido nucleico e de vetor de expressão, vetor de expressão, célula hospedeira, e, métodos para produzir proteína heterodimérica biespecífica e para tratar câncer em um paciente |
TWI791471B (zh) | 2016-11-15 | 2023-02-11 | 美商建南德克公司 | 用於用抗cd20/抗cd3雙特異性抗體進行治療之給藥 |
US20200078400A1 (en) * | 2016-12-03 | 2020-03-12 | Juno Therapeutics, Inc. | Methods for determining car-t cells dosing |
KR20180090600A (ko) | 2017-02-03 | 2018-08-13 | 주식회사 대유위니아 | 전기밥솥 |
EP3409322A1 (en) * | 2017-06-01 | 2018-12-05 | F. Hoffmann-La Roche AG | Treatment method |
CA3067603A1 (en) | 2017-06-30 | 2019-01-03 | Xencor, Inc. | Targeted heterodimeric fc fusion proteins containing il-15/il-15ra and antigen binding domains |
JP7288431B2 (ja) * | 2017-08-30 | 2023-06-07 | ブリストル-マイヤーズ スクイブ カンパニー | グルココルチコイドのインビボ投与によって介在される薬力学的応答をモニタリングするための方法 |
US11564946B2 (en) | 2017-11-01 | 2023-01-31 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
AU2018366199A1 (en) | 2017-11-08 | 2020-05-28 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-PD-1 sequences |
US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
US10537585B2 (en) | 2017-12-18 | 2020-01-21 | Dexcel Pharma Technologies Ltd. | Compositions comprising dexamethasone |
AU2018390418B2 (en) | 2017-12-19 | 2023-12-21 | Xencor, Inc. | Engineered IL-2 Fc fusion proteins |
MX2020008289A (es) | 2018-02-08 | 2020-09-25 | Genentech Inc | Moleculas biespecificas de union al antigeno y metodos de uso. |
AU2019247415A1 (en) | 2018-04-04 | 2020-10-22 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
WO2019204655A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
CA3097593A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof |
MA53822A (fr) | 2018-10-03 | 2021-08-11 | Xencor Inc | Protéines de fusion fc hétérodimères d'il -12 |
KR20210134725A (ko) | 2019-03-01 | 2021-11-10 | 젠코어 인코포레이티드 | Enpp3과 cd3에 결합하는 이종이량체 항체 |
JOP20210298A1 (ar) | 2019-05-14 | 2023-01-30 | Provention Bio Inc | طرق وتركيبات للوقاية من مرض السكري من النوع الأول |
RU2738802C1 (ru) * | 2019-08-21 | 2020-12-17 | Общество с ограниченной ответственностью "Международный Биотехнологический Центр "Генериум" | Определяющие комплементарность участки для связывания cd3 и содержащая их биспецифическая антигенсвязывающая молекула |
IL293423A (en) | 2019-12-13 | 2022-07-01 | Genentech Inc | Anti-ly6g6d antibodies and methods of use |
US11919956B2 (en) | 2020-05-14 | 2024-03-05 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (PSMA) and CD3 |
IL298999A (en) | 2020-06-11 | 2023-02-01 | Provention Bio Inc | Methods and compositions for the prevention of type 1 diabetes |
KR102607909B1 (ko) | 2020-08-19 | 2023-12-01 | 젠코어 인코포레이티드 | 항-cd28 조성물 |
US11739144B2 (en) | 2021-03-09 | 2023-08-29 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and CLDN6 |
JP2024509274A (ja) | 2021-03-10 | 2024-02-29 | ゼンコア インコーポレイテッド | Cd3及びgpc3に結合するヘテロ二量体抗体 |
WO2023057650A1 (en) | 2021-10-10 | 2023-04-13 | Centre Hospitalier Universitaire Vaudois (Chuv) | A method for predicting side effects of drugs and vaccines |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002512020A (ja) * | 1998-04-21 | 2002-04-23 | マイクロメット アーゲー | Cd19×cd3特異的ポリペプチドおよびその使用 |
JP2009519257A (ja) * | 2005-12-16 | 2009-05-14 | ミクロメット・アクチェンゲゼルシャフト | 腫瘍性疾患を処置するための手段および方法 |
WO2010052014A1 (en) * | 2008-11-07 | 2010-05-14 | Micromet Ag | Treatment of acute lymphoblastic leukemia |
JP2013508439A (ja) * | 2009-10-27 | 2013-03-07 | マイクロメット アクチェンゲゼルシャフト | CD19xCD3二重特異性抗体を投与するための投与計画 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3856559T2 (de) | 1987-05-21 | 2004-04-29 | Micromet Ag | Multifunktionelle Proteine mit vorbestimmter Zielsetzung |
US20070224191A1 (en) | 2002-12-05 | 2007-09-27 | Pdl Biopharma, Inc. | Methods of treatment of Ulcerative Colitis and Crohn's disease with anti-CD3 antibodies |
CN100509850C (zh) | 2003-05-31 | 2009-07-08 | 麦克罗梅特股份公司 | 用于治疗b细胞相关疾病的包含双特异性抗cd3、抗cd19抗体构建体的药物组合物 |
ES2417065T3 (es) | 2005-04-26 | 2013-08-05 | Trion Pharma Gmbh | Combinación de anticuerpos con glucocorticoides para el tratamiento del cáncer |
CN101331151A (zh) * | 2005-12-16 | 2008-12-24 | 麦克罗梅特股份公司 | 治疗肿瘤性疾病的方式和方法 |
AU2008234019B2 (en) | 2007-04-03 | 2014-05-29 | Amgen Research (Munich) Gmbh | Cross-species-specific bispecific binders |
WO2008119565A2 (en) | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific binding domain |
RS58217B1 (sr) | 2007-04-03 | 2019-03-29 | Amgen Res Munich Gmbh | Interspecijski specifičan vezujući domen |
EP2225275A4 (en) | 2007-11-28 | 2013-04-03 | Medimmune Llc | PROTEIN FORMULATION |
PL3412687T3 (pl) | 2010-10-27 | 2020-07-27 | Amgen Research (Munich) Gmbh | Sposoby leczenia dlbcl |
FI2637670T4 (fi) | 2010-11-10 | 2024-03-19 | Amgen Research Munich Gmbh | Cd3-spesifisten sitoutumisdomeenien aiheuttamien haittavaikutusten estäminen |
-
2011
- 2011-10-27 FI FIEP11788077.3T patent/FI2637670T4/fi active
- 2011-10-27 WO PCT/EP2011/068862 patent/WO2012062596A1/en active Application Filing
- 2011-10-27 PL PL11788077.3T patent/PL2637670T5/pl unknown
- 2011-10-27 CN CN201180064622.5A patent/CN103533943B/zh active Active
- 2011-10-27 KR KR1020137014669A patent/KR101891845B1/ko active IP Right Grant
- 2011-10-27 SG SG2013034731A patent/SG190174A1/en unknown
- 2011-10-27 ES ES17159560T patent/ES2842937T3/es active Active
- 2011-10-27 LT LTEP11788077.3T patent/LT2637670T/lt unknown
- 2011-10-27 ES ES11788077.3T patent/ES2627538T3/es active Active
- 2011-10-27 JP JP2013538125A patent/JP6023717B2/ja active Active
- 2011-10-27 EP EP20209362.1A patent/EP3831386A1/en active Pending
- 2011-10-27 NZ NZ610034A patent/NZ610034A/en unknown
- 2011-10-27 CA CA2816668A patent/CA2816668C/en active Active
- 2011-10-27 RS RS20170458A patent/RS55995B2/sr unknown
- 2011-10-27 CN CN201810044039.1A patent/CN108403702A/zh active Pending
- 2011-10-27 SI SI201131196T patent/SI2637670T2/sl unknown
- 2011-10-27 HU HUE11788077A patent/HUE032782T2/en unknown
- 2011-10-27 EA EA201390621A patent/EA026075B1/ru not_active IP Right Cessation
- 2011-10-27 UA UAA201307130A patent/UA113397C2/uk unknown
- 2011-10-27 AU AU2011328393A patent/AU2011328393B2/en active Active
- 2011-10-27 PT PT117880773T patent/PT2637670T/pt unknown
- 2011-10-27 US US13/884,497 patent/US10130638B2/en active Active
- 2011-10-27 EP EP17159560.6A patent/EP3228315B1/en active Active
- 2011-10-27 EP EP11788077.3A patent/EP2637670B2/en active Active
- 2011-10-27 DK DK11788077.3T patent/DK2637670T4/da active
- 2011-10-27 SG SG10201508789TA patent/SG10201508789TA/en unknown
- 2011-10-27 ME MEP-2017-104A patent/ME02722B/me unknown
- 2011-10-27 HR HRP20170814TT patent/HRP20170814T4/hr unknown
- 2011-10-27 MY MYPI2013001611A patent/MY173177A/en unknown
-
2013
- 2013-05-09 IL IL226268A patent/IL226268B/en active IP Right Grant
- 2013-05-09 CL CL2013001287A patent/CL2013001287A1/es unknown
- 2013-06-10 MA MA35999A patent/MA34726B1/fr unknown
- 2013-06-10 TN TNP2013000250A patent/TN2013000250A1/fr unknown
- 2013-06-10 CR CR20130278A patent/CR20130278A/es unknown
-
2016
- 2016-07-06 JP JP2016133918A patent/JP6189491B2/ja active Active
-
2017
- 2017-03-29 AU AU2017202079A patent/AU2017202079B2/en active Active
- 2017-05-08 CY CY20171100491T patent/CY1118894T1/el unknown
-
2018
- 2018-01-25 IL IL257164A patent/IL257164B/en active IP Right Grant
- 2018-02-07 AU AU2018200915A patent/AU2018200915B2/en active Active
- 2018-10-11 US US16/157,985 patent/US11633408B2/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002512020A (ja) * | 1998-04-21 | 2002-04-23 | マイクロメット アーゲー | Cd19×cd3特異的ポリペプチドおよびその使用 |
JP2009519257A (ja) * | 2005-12-16 | 2009-05-14 | ミクロメット・アクチェンゲゼルシャフト | 腫瘍性疾患を処置するための手段および方法 |
WO2010052014A1 (en) * | 2008-11-07 | 2010-05-14 | Micromet Ag | Treatment of acute lymphoblastic leukemia |
JP2013508439A (ja) * | 2009-10-27 | 2013-03-07 | マイクロメット アクチェンゲゼルシャフト | CD19xCD3二重特異性抗体を投与するための投与計画 |
Non-Patent Citations (1)
Title |
---|
CANCER IMMUNOL IMMUNOTHER, vol. 56, JPN6017015170, 2007, pages 1551 - 1563, ISSN: 0003599801 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6189491B2 (ja) | Cd3特異的結合ドメインによって引き起こされる有害作用の予防 | |
US11579142B2 (en) | Dosage regimen for administering a CD19xCD3 bispecific antibody to patients at risk for potential adverse effects | |
KR20220158821A (ko) | Il-4r 길항제를 투여함에 의해 아토피 피부염을 치료하기 위한 방법 | |
MX2011003335A (es) | Composicion para tratar enfermedad. | |
AU2012350429A1 (en) | Prevention of adverse effects caused by EpCAMxCD3 bispecific antibodies | |
US9486475B2 (en) | PPS for the prevention of potential adverse effects caused by CD3 specific binding domains | |
JP5963233B2 (ja) | Htlv−1関連脊髄症を治療または予防するための医薬および前記医薬を用いた抗体療法の治療効果の確認方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170414 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170501 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20170718 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170802 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6189491 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |